Proliferation and differentiation in the human breast during pregnancy

Using multiple immunofluorescence labelling on human breast tissues obtaine d and freshly frozen at the 12th, 15th, and 18th weeks of pregnancy, we hav e shown that markers of mammary functional differentiation, milk proteins ( beta -casein and kappa -casein), are synthesised by actively cycling (Ki67 positive) as well as non-cycling (Ki67 negative) cells. These results demon strate that functional differentiation/maturation does not coincide with lo ss of proliferative potential in human mammary luminal epithelial cells. In addition, we have examined expression patterns of integrin subunits (alpha 1, alpha2, alpha3, alpha6, beta1, and beta4) and extracellular matrix compo nents (laminin, fibronectin, collagen I, and collagen IV), since they have been shown to exert influences on mammary differentiation and morphogenesis in vitro. Compared to human breast tissues obtained from non-pregnant wome n, a decrease in alpha2 labelling on luminal epithelial cells was observed, particularly in expanding acini that showed abundant Ki67 positivity. The expression patterns of other integrin subunits, however, did not change, in dicating that the expression patterns of most integrins existing Drier to p regnancy are sufficient to support the morphological and functional develop ment associated with milk protein synthesis.